Carbon-Based Weakly Coordinating Anions: Molecular Design, Synthesis and Applications.

Although carbanions, which are usually regarded as reactive species and powerful metalation reagents, can be stabilized through choice of the substitution pattern, they have rarely been considered for the design of weakly coordinating anions (WCA).  Here, we report on an evaluation of the potential of a series of differently substituted carbanions to serve as WCA by computational methods. This led us to the synthesize the water- and air-stable allyl anion 1 with triflyl and 3,5-bis(trifluoromethyl)phenyl (ArF) moieties, which can be isolated in high yields even on a gram-scale. Single crystal X-ray crystallography and NMR studies confirmed the weak coordination ability of the anion by showing negligible or only weak interactions with different cations. This property enabled the application of 1 in the stabilization of reactive group 14 and 15 cations. In addition to the crystallization of a phosphenium cation, the first all-carbon salt with a non-aromatic carbanion is reported, which revealed to be a convenient reagent for hydride abstraction such as from silanes. Overall, this work demonstrates the so far untapped potential of carbanions as WCA, that are accessible with a variety of different cations for various applications.

P,N-Coordinating Ylide-Functionalized Phosphines (NYPhos): A Ligand Platform for the Selective Monoarylation of Small Nucleophiles.

Palladium-catalyzed coupling reactions of small nucleophiles are of great interest, but challenging due to difficulties in selectivity control. Herein, we report the development of a new platform of P,N-ligands consisting of ylide-functionalized phosphines with aminophosphonium groups (NYPhos) to address this challenge. These phosphine ligands are easily accessible in a wide structural diversity with highly modular electronic and steric properties. Based on a family of 14 ligands the selective monoarylation of acetone as well as other challenging ketones and amides was accomplished with record-setting activities even for aryl chlorides at room temperature including late-stage functionalizations of drug molecules. Moreover, ammonia and other small primary amines could be coupled at mild conditions. Isolation and structure analyses of palladium complexes within the catalytic cycle confirmed the P,N-coordination mode necessary to reach the observed selectivities and proved the facile adjustability of the N-donor strength, which is beneficial for the targeted design of tailored P,N-ligands for future applications.

Ligand Exchange at Carbon: Synthetic Entry to Elusive Species and Versatile Reagents.

How different is carbon compared to other elements in the periodic table? Can carbon compounds be regarded as coordination complexes with carbon as the central element undergoing a facile exchange of its ligands? Although carbon clearly plays a special role among the elements of the periodic table, recent studies have drawn parallels between the bonding situation and the reactivity of carbon compounds to transition metal complexes. This Perspective summarizes recent reports about ylidic and zwitterionic compounds that were shown to exhibit ambiguous bonding situations that can be interpreted as donor-acceptor interactions similar to the bond between a metal and a neutral ligand. Based on this conception, ligand exchange reactions prototypical of transition metal complexes were realized at carbon atoms, enabling new synthetic strategies for the synthesis of reactive species and building blocks. In particular, the exchange of N2, CO, and phosphine ligands led to the development of a mild method for accessing new compounds and reagents with unusual properties, such as vinylidene ketenes or stable ketenyl anions, that open up a diverse but still poorly explored follow-up chemistry.

The Cyanoketenyl Anion [NC3O].

Cumulenes and heterocumulenes with three or more cumulative multiple bonds are usually reactive species that serve as valuable building blocks for more complex molecules but tend to isomerize or cyclize and therefore are difficult to isolate. Using a mild ligand exchange reaction at the carbon in α-metalated ylides, we have now succeeded in the synthesis and gram-scale isolation of the elusive cyanoketenyl anion [NC3O]-. Despite its assumed cumulene-like structure and the delocalization of the negative charge across the whole 5-atom molecule, it features a bent geometry with a nucleophilic central carbon atom. Computational studies reveal an ambiguous bonding situation in the anion, which can be illustrated only by a combination of different resonance structures. Nonetheless, the anion features remarkable stability, thus allowing the storage of its potassium-crown ether salt and its application as a highly functional synthetic building block. The cyanoketenyl anion readily reacts with a series of small molecules to form more complex organic compounds, including industrially valuable compounds such as cyanoacetate. This work demonstrated that reactive species can be generated by novel synthesis methods and open up atom-economic pathways to complex compounds from small abundant molecules.

Phosphinoyl-Substituted Ketenyl Anions: Synthesis and Substituent Effects on the Structural Properties.

Ketenyl anions are versatile intermediates in synthetic chemistry and have recently become accessible as isolable reagents from metalated ylides by exchange of the phosphine with CO. Herein, we report on a systematic study of substituent effects on the structure and bonding situation in ketenyl anions. A series of phosphinoyl-substituted ketenyl anions {[R2P(X)CCO]- with X = O, NTol, S, Se} were prepared by carbonylation of the corresponding yldiides and isolated as their corresponding potassium salts. NMR and IR spectroscopic analyses together with computational studies demonstrate that the more electron-withdrawing oxo- and iminophosphinoyl substituents increase the s-character in the bond to the ketene moiety and hence the ynolate character of the anion. This trend is particularly seen in solution, whereas the solid-state properties are influenced by packing effects affecting the bonding situation.

From a mercury(II) bis(yldiide) complex to actinide yldiides.

The bis(yldiide) mercury complex, (L-Hg-L) [L = C(PPh3)P(S)Ph2], is prepared from the corresponding potassium yldiide and used to access the first substituted yldiide actinide complexes [(C5Me5)2An(L)(Cl)] (An = U, Th) via salt metathesis. Compared to previously reported phosphinocarbene complexes, the complexes exhibit long actinide-carbon distances, which can be explained by the strong polarization of the π-electron density toward carbon.

Selectivity Control of the Ligand Exchange at Carbon in α-Metallated Ylides as a Route to Ketenyl Anions.

α-Metallated ylides have recently been reported to undergo phosphine by CO exchange at the ylidic carbon atom to form isolable ketenyl anions. Systematic studies on the tosyl-substituted yldiides, R3 P=C(M)Ts (M=Li, Na, K), now reveal that carbonylation may lead to a competing metal salt (MTs) elimination. This side-reaction can be controlled by the choice of phosphine, metal cation, solvent and co-ligands, thus enabling the selective isolation of the ketenyl anion [Ts-CCO]M (2-M). Complexation of 2-Na by crown ether or cryptand allowed structure elucidation of the first free ketenyl anion [Ts-CCO]- , which showed an almost linear Ts-C-C linkage indicative for a pronounced ynolate character. However, DFT studies support a high charge at the ketenyl carbon atom, which is reflected in the selective carbon-centered reactivity. Overall, the present study provides important information on the selectivity control of ketenyl anion formation which will be crucial for future applications.

Probing the donor strength of yldiide ligands: synthesis, structure and reactivity of rhodium complexes with a PCylideN pincer ligand.

Control of the metal ligand interaction by changes in the ligand protonation state is vital to many catalytic transformations based on metal-ligand cooperativity. Herein, we report on the coordination chemistry of a new PCy(H)N pincer ligand with a central ylide as donor site, which through deprotonation to the corresponding yldiide changes from a neutral L3-type ligand to an anionic L2X-type PCYN ligand. The isolation of a series of rhodium complexes showed that the strong donor ability of the neutral ylide PCY(H)N is further increased upon deprotonation, as evidenced by one of the lowest reported CO stretching frequencies in complex [(PCYN)Rh(CO)] (2) compared to other known rhodium carbonyl complexes. DFT calculations revealed that the high donor ability mostly results from the antibonding interaction of the pπ orbital at the ylide with the d xz orbital at rhodium, which enhances the backdonation into the π* orbital of the CO ligand. This unique interaction results in a rather long metal-carbon bond, but still a strong activation of the CO ligand in order to minimize repulsion between the filled orbitals at the rhodium and the ylide ligand. Accordingly, CO by phosphine replacement leads to a strong deviation from the square-planar geometry in the analogous phosphine complexes [(PCYN)Rh(PR3)] and an unusual reactivity with small alkyl halides, which upon oxidative addition add to the CO ligand, before inserting into the P-C bond in the pincer ligand. These results demonstrate the unique donor strength of yldiide ligands and their potential in the activation of strong bonds.

Correlation of Experimental and Calculated Reaction Enthalpies with Ligand Donor Strengths.

Ylide-functionalized phosphines (YPhos) have recently proven to be strongly donating ligands that enable high catalyst activities in gold(I)-mediated transformations. We now report on a calorimetric study dealing with the [Au(YPhos)Cl] system and assess YPhos-Au bond dissociation enthalpies (BDE). Comparison with other commonly used phosphines confirmed the high binding strengths of the YPhos ligands. Furthermore, the values of the reaction enthalpies were shown to correlate with the electronic properties of the ligands measured via the Tolman electronic parameter or the calculated molecular electrostatic potential at phosphorus. Notably, the reaction enthalpies can conveniently be derived by computational methods, thus making these easy-to-obtain descriptors for ligand donor property quantification.

Inverting the Electronic Structure of Diylidylgermylenes by Backbone Modification.

Owing to the strong electron-donating ability of ylide substituents, diylidyltetrylenes are usually highly nucleophilic species with strong donor capacities. Here, we demonstrate that their electronic properties are in fact highly flexible and can be effectively tuned through variation of the substituent in the ylide backbone. Initial density functional theory studies showed that cyano groups are particularly capable in lowering the LUMO energy of diylidyl germylenes thus turning these usually highly nucleophilic species into electrophilic compounds. This was confirmed by experimental studies. Attempts to synthesize the germylene (YCN )2 Ge [with YCN =Ph3 P-(C)-CN] from the corresponding metalated ylide YCN K selectively led to germanide [(YCN )3 Ge)K]2 thus reflecting the electrophilic nature of the intermediate formed germylene. XRD analysis of single crystals of (YCN )2 Ge - serendipitously obtained through protonative cleavage of one ylide from the germanide - revealed a monomeric structure with rather long Ge-ylide linkages, which corroborates well with a pure single bond and no stabilization of the empty pπ orbital at germanium through π bonding. The germanide exhibits methanide-like reactivity towards chalcogens but a likewise weak Ge-C bond as demonstrated by the insertion of carbon dioxide.

From a Fluorenyl Substituted Ylide-Functionalized Phosphine to a Neutral Phosphide via P-C Bond Cleavage.

Bulky ylide-substituted phosphines have recently found application as potent ligands in homogeneous catalysis. The attempted synthesis of the ylide-substituted fluorenylphosphine YPh P(Cy)Flu [YPh =Cy3 P(Ph)C; Flu=9-methylfluorenyl] now resulted in the unexpected elimination of 9-methylenefluorene during the deprotonation step of the intermediary α-phosphino phosphonium salt to yield the secondary ylide-substituted phosphine YPh P(Cy)H. This phosphine underwent formal H2 elimination under basic conditions to form a cyclic phosphonium ylide with a P-C-P-C four-membered ring via deprotonation of one cyclohexyl group of the PCy3 moiety. Upon coordination to transition metals the secondary ylidylphosphine forms a neutral phosphide ligand by shift of the proton into the ylide-backbone and formation of zwitterionic metal complexes.

Thiophosphinoyl-Tethered Ylide-Substituted Heavier Carbenes: Synthesis, Structures and Stabilities.

The synthesis and structure analysis of a series of mono and diylide-substituted tetrylenes of type YEX and Y2 E (E=Ge, Sn, Pb; X=Cl or Br) using a thiophosphinoyl-tethered metallated ylide (Y=Ph2 P(S)-C-P(pip)Ph2 with pip=piperidyl) is reported, amongst the first ylide-substituted plumbylenes. The tetrylenes feature distinct trends in the spectroscopic and structural properties of the ylide ligand with increasing atomic number of the tetrel element. For instance, an increasingly high-field shifted signal for the thiophosphinoyl group is observed in the 31 P{1 H} NMR spectrum as a consequence of the increasing polarity of the element-carbon bond, which likewise results in a shortening of the ylidic C-P bond in the solid-state structure. The diylidyltetrylenes are unstable towards transylidation forming the mono(ylide)tetrylenes when treated with the tetrel dihalides according to the stability trend: Y2 Pb

Computer-Driven Development of Ylide Functionalized Phosphines for Palladium-Catalyzed Hiyama Couplings.

Palladium-catalyzed couplings of silicon enolates with aryl electrophiles are of great synthetic utility, but often limited to expensive bromide substrates. A comparative experimental study confirmed that none of the established ligand systems allows to couple inexpensive aryl chlorides with α-trimethylsilyl alkylnitriles. In contrast, ylide functionalized phosphines (YPhos) led to encouraging results. A statistical model was developed that correlates the reaction yields with ligand features. It was employed to predict catalyst structures with superior performance. With this cheminformatics approach, YPhos ligands were tailored specifically to the demands of Hiyama couplings. The newly synthesized ligands displayed record-setting activities, enabling the elusive coupling of aryl chlorides with α-trimethylsilyl alkyl nitriles. The preparative utility of the catalyst system was demonstrated by the synthesis of pharmaceutically meaningful α-aryl alkylnitriles, α-arylcarbonyls and biaryls.

Transition metal-free ketene formation from carbon monoxide through isolable ketenyl anions.

The capacity of transition metals to bind and transform carbon monoxide (CO) is critical to its use in many chemical processes as a sustainable, inexpensive C1 building block. By contrast, only few s- and p-block element compounds bind and activate CO, and conversion of CO into useful carbonyl-containing organic compounds in such cases remains elusive. We report that metalated phosphorus ylides provide facile access to ketenyl anions ([RC=C=O]-) by phosphine displacement with CO. These anions are very stable and storable reagents with a distinctive electronic structure between that of the prototypical ketene (H2C=C=O) and that of ethynol (HC≡C-OH). Nonetheless, the ketenyl anions selectively react with a range of electrophiles at the carbon atom, thus offering high-yielding and versatile access to ketenes and related compounds.

Formation of exceptional monomeric YPhos-PdCl2 complexes with high activities in coupling reactions.

The use of well-defined palladium(ii) complexes as precatalysts for C-X cross-coupling reactions has improved the use of palladium catalysts in organic synthesis including large-scale processes. Whereas sophisticated Pd(ii) precursors have been developed in the past years to facilitate catalyst activation as well as the handling of systems with more advanced monophosphine ligands, we herein report that simple PdCl2 complexes function as efficient precatalysts for ylide-substituted phosphines (YPhos). These complexes are readily synthesized from PdCl2 sources and form unprecedented monomeric PdCl2 complexes without the need for any additional coligand. Instead, these structures are stabilized through a unique bonding motif, in which the YPhos ligands bind to the metal through the adjacent phosphine and ylidic carbon site. DFT calculations showed that these bonds are both dative interactions with the stronger interaction originating from the electron-rich phosphine donor. This bonding mode leads to a remarkable stability even towards air and moisture. Nonetheless, the complexes readily form monoligated LPd(0) complexes and thus the active palladium(0) species in coupling reactions. Accordingly, the YPhos-PdCl2 complexes serve as highly efficient precatalysts for a series of C-C and C-X coupling reactions. Despite their simplicity they can compete with the efficiency of more complex and less stable precatalysts.

Reaction of lithium hexamethyldisilazide (LiHMDS) with water at ultracold conditions.

Alkali metal amides are highly reactive reagents that are broadly applied as strong bases in organic synthesis. Here, we use a combined helium nanodroplet IR spectroscopic and theoretical (DFT calculation) study to show that the reaction of the model compound lithium hexamethyldisilazide (LiHMDS) with water is close to barrierless even at ultra-cold conditions. Upon complex formation of dimeric (LiHMDS)2 with water in helium nanodroplets as ultra-cold nano-reactors (0.37 K) we observed the reaction product (LiOH)2(HMDS)2. This can be rationalized as aggregation induced reation upon stepwise addition of water. With increasing water partial pressure, only the product (LiOH)2(HMDS)2 is observed experimentally. This implies that the large interaction energy (69 kJ mol-1) of (LiHMDS)2 with water is sufficient to overcome the follow-up reaction barriers, in spite of the rapid cooling rates in He nanodroplets.

From Stable PH-Ylides to α-Carbanionic Phosphines as Ligands for Zwitterionic Catalysts.

Although ylides are commonly used reagents in organic synthesis, the parent methylphosphine MePH2 only exists in its phosphine form in the condensed phase. Its ylide tautomer H3 P+ -CH2 - is considerably higher in energy. Here, we report on the formation of bis(sulfonyl)methyl-substituted phosphines of the type (RO2 S)2 C(H)-PR2, which form stable PH ylides under ambient conditions, amongst the first examples of an acyclic phosphine which only exists in its PH ylide form. Depending on the exact substitution pattern the phosphines form an equilibrium between the PH ylide and the phosphine form or exist as one of both extremes. These phosphines were found to be ideal starting systems for the facile formation of α-carbanionic phosphines. The carbanion-functionalization leads to a switch from electron-poor to highly electron-rich phosphines with strong donor abilities and high basicities. Thus, the phosphines readily react with different electrophiles exclusively at the phosphorus atom and not at the carbanionic center. Furthermore, the anionic nature of the phosphines allows the formation of zwitterionic complexes as demonstrated by the isolation of a gold(I) complex with a cationic metal center. The cationic gold center allows for catalytic activity in the hydroamination of alkyne without requiring a further activation step.

Ylide-Substituted Phosphines: A Platform of Strong Donor Ligands for Gold Catalysis and Palladium-Catalyzed Coupling Reactions.

The development of homogeneous catalysts is strongly connected to the design of new, sophisticated ligands, which resolve limitations of a given reaction protocol by manipulating the electronic properties of the metal and its spatial environment. Phosphines are a privileged class of ligands that find applications in many catalytic transformations, ranging from hydrogenation reactions to hydroformylation and coupling chemistry. For many years, chemists have been trying to improve the efficiency, selectivity, and application of coupling reactions. The use of highly electron-rich and bulky phosphines was often associated with increased selectivity and efficiency and led to the development of a vast variety of electron-rich alkyl-substituted phosphines. However, this concept of increasing the ligand donor strength reaches its limits with the use of trialkyl-substituted phosphines with tri-tert-butylphosphine thus being one of the most active ligands for many years. In the course of our research efforts to use the special donor strength of ylides to stabilize electron-deficient, low-valent main group compounds, we realized that ylide-substituted phosphine (YPhos) ligands possess remarkably strong donor abilities. Moreover, the YPhos ligands are highly tunable by changing the nature of the groups on the phosphonium, phosphine, or central ylidic carbon atom. We thus obtained a ligand platform with donor capabilities ranging from PCy3 to even stronger donor abilities than N-heterocyclic carbenes, while being more sterically demanding than simple phosphines as well as many well-known biarylphosphine ligands.These properties led us to explore the applicability of the YPhos ligands in catalysis. In a series of recent reports, our group applied YPhos ligands in gold and palladium catalyzed reactions at catalytic loadings applicable for medium- to large-scale applications. The increased donor strength and unique architecture allowed for remarkable activities in a series of transformations at mild reactions conditions. For gold(I)-catalyzed reactions, we obtained turnover numbers (TONs) for the hydroamination of phenylacetylene with aniline of over 20 000. Also, more complex reactions were easily catalyzed with efficiencies greater than those of other known gold(I) catalysts. Similar efficacies were found in a series of palladium-catalyzed coupling reactions. In Buchwald-Hartwig aminations, unprecedented activities for the amination of aryl chlorides were reached at room temperature. The speed of formation of the catalytically active mono-YPhos palladium species allowed for some of the amination reactions to be completed in only a few minutes. Adjustment of the ligand design enabled the use of a large variety of different aryl and alkyl amines of different steric demands. Furthermore, the YPhos ligands in general showed high activities and selectivity in the coupling of a variety of carbon nucleophiles with aryl chlorides, bromides, and triflates. This enabled the development of efficient reaction protocols for the α-arylation of unhindered ketones and the coupling of Grignard and zinc reagents as well as the first efficient coupling of chloroarenes with alkyllithium compounds. This Account summarizes the recent development of YPhos ligands and their application in gold and palladium catalysis. We also hope to stimulate further use of this ligand platform in catalysis in the future.

Ylide-Stabilized Phosphenium Cations: Impact of the Substitution Pattern on the Coordination Chemistry.

Although N-heterocyclic phosphenium (NHP) cations have received considerable research interest due to their application in organocatalysis, including asymmetric synthesis, phosphenium cations with other substitution patterns have hardly been explored. Herein, the preparation of a series of ylide-substituted cations of type [YPR]+ (with Y=Ph3 PC(Ph), R=Ph, Cy or Y) and their structural and coordination properties are reported. Although the diylide-substituted cation forms spontaneous from the chlorophosphine precursor, the monoylidylphosphenium ions required the addition of a halide-abstraction reagent. The molecular structures of the cations reflected the different degrees of electron donation from the ylide to the phosphorus center depending on the second substituent. Molecular orbital analysis confirmed the stronger donor properties of the ylide systems compared to NHPs with the mono-ylide substituted cations featuring a more pronounced electrophilicity. This was mirrored by the reaction of the cations towards gold chloride, in which only the diylide-substituted cation [Y2 P]+ formed the expected LAuCl]+ complex, while the monoylide-substituted compounds reacted to the chlorophosphine ligands by transfer of the chloride from gold to the phosphorus center. These results demonstrate the tunability of ylide-functionalized phosphorus cations, which should allow for further applications in coordination chemistry in the future.

Synthesis, Crystal and Electronic Structures of a Thiophosphinoyl- and Amino-Substituted Metallated Ylide.

Invited for this month's cover is the group of Viktoria H. Gessner at the Ruhr-University in Bochum (Germany). The cover shows the structure of the newly reported, isolated metallated ylide. Due to the high negative charge at the ylidic carbon center this compound is "on fire", but can be stabilized by smart molecular design. Structure analyses of the different alkali metal complexes combined with computational studies provide insights into the electronic structure of the compounds Read the full text of their Communication at 10.1002/open.202100178.